{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:20:09Z","timestamp":1783178409996,"version":"3.54.6"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004861","name":"Mackay Memorial Hospital","doi-asserted-by":"publisher","award":["MMH-E-100-08 to MMH-E-109-08"],"award-info":[{"award-number":["MMH-E-100-08 to MMH-E-109-08"]}],"id":[{"id":"10.13039\/501100004861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Studies have shown that elevated plasma levels of platelet-derived soluble TREM-like transcript-1 (sTLT-1) are associated with an unfavorable outcome in patients with septic shock. However, the underlying molecular mechanisms are not well defined. This research aimed to study the role of sTLT-1 in mediating immune dysfunction during the development of sepsis. Our study demonstrated that patients with septic shock have significantly higher plasma concentrations of sTLT-1, whereas sTLT-1 is not detectable in healthy subjects. Plasma concentrations of sTLT-1 were correlated with the degree of immunosuppressive parameters in monocytes from patients with septic shock. sTLT-1 can first activate monocytes by binding to the TLR4\/MD2 complex but subsequently induce immunosuppressive phenotypes in monocytes. Blocking Abs against TLR4 and MD2 led to a significant decrease in sTLT-1\u2013induced activation. Treatment with an anti\u2013TLT-1 Ab also significantly reduces sTLT-1 binding to monocytes and proinflammatory cytokine secretion in a mouse model of endotoxemia. sTLT-1 acts as an endogenous damage-associated molecular pattern molecule, triggering the activation of monocytes through the TLR4\/MD2 complex followed by sustained immune suppression. This process plays a crucial role in the development of sepsis-associated pathophysiology. Our findings outline, to our knowledge, a novel pathway whereby platelets counteract immune dynamics against infection through sTLT-1.<\/jats:p>","DOI":"10.4049\/jimmunol.2200222","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T15:08:18Z","timestamp":1679670498000},"page":"1351-1362","source":"Crossref","is-referenced-by-count":10,"title":["Soluble TREM-like Transcript-1 Acts as a Damage-Associated Molecular Pattern through the TLR4\/MD2 Pathway Contributing to Immune Dysregulation during Sepsis"],"prefix":"10.1093","volume":"210","author":[{"given":"Chia-Ming","family":"Chang","sequence":"first","affiliation":[{"name":"Ascendo Biotechnology, Inc. , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8166-2011","authenticated-orcid":false,"given":"Kuang-Hua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University , Taipei,","place":["Taiwan"]},{"name":"Department of Critical Care Medicine, MacKay Memorial Hospital , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-2407","authenticated-orcid":false,"given":"Tsai-Yin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-3026","authenticated-orcid":false,"given":"Meng-Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"Ascendo Biotechnology, Inc. , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Ascendo Biotechnology, Inc. , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9798-8355","authenticated-orcid":false,"given":"Yen-Ta","family":"Lu","sequence":"additional","affiliation":[{"name":"Ascendo Biotechnology, Inc. , Taipei,","place":["Taiwan"]},{"name":"Chest Division, Medical Department, MacKay Memorial Hospital , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"2025021008041209200_r1","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1056\/NEJMoa1415236","article-title":"Systemic inflammatory response syndrome criteria in defining severe sepsis","volume":"372","author":"Kaukonen","year":"2015","journal-title":"N. 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